Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Digestive System Diseases

Nutritional and Metabolic Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Syndrome

Leukemia

Neutropenia

Bone Marrow Failure Disorders

Pancytopenia

Disease Susceptibility

Congenital Bone Marrow Failure Syndromes

Shwachman-Diamond Syndrome

Exocrine Pancreatic Insufficiency

Bone Marrow Diseases

Lipomatosis

Lipomatosis, Multiple Symmetrical

Pancreatic Diseases

Gastrointestinal Diseases

Hematologic Diseases

Metabolism, Inborn Errors

Lipid Metabolism, Inborn Errors

Metabolic Diseases

Lipid Metabolism Disorders

Skin Diseases

Granulocytopenia

Multiple Symmetric Lipomatosis

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

Akiko Shimamura, MD, PhD

Karyn Brundige

Taizo Nakano, MD

Christopher R Reilly, MD

Kasiani Myers, MD

Sara Loveless, RN

Shwachman-Diamond syndrome (SDS) is a genetic condition characterized by bone marrow failure, medical co-morbidities, and leukemia predisposition. SDS-Like patients share clinical features with SDS but lack mutations in known SDS genes. Since SDS/SDS-Like syndromes are rare diseases, data are sparse regarding the clinical features, natural history, clinical outcomes with current management, and treatment. For this reason, the SDS Registry was formed to collect clinical data from medical records and to bank biological samples with the goal of understanding SDS/SDS-Like diseases to develop better treatments and improve the health of patients with these conditions.

The Shwachman-Diamond Syndrome Registry (SDSR) is dedicated to accelerating research and treatment for SDS to improve survival and quality of life for all patients with the disease. The SDSR is run jointly by Boston Children's Hospital and Cincinnati Children's Hospital Medical Center.

Objective and Aims:

The long term goals of the Registry are to improve diagnosis, inform medical management, and to develop better treatments for SDS and SDS-Like disorders.

To achieve these objectives, the Registry has the following specific aims:

* Characterize the natural history, medical complications, and treatment outcomes for patients with SDS and SDS-Like disorders.
* Investigate the molecular and genetic pathogenesis of SDS/SDS-Like conditions and their complications such as marrow failure and clonal evolution.
* Identify new genes causing SDS/SDS-Like conditions.
* Provide education on the diagnosis, medical management and treatment of SDS for patients, families and the medical/scientific community.

Methods: The SDSR collects information from medical records and biological samples. Samples for the SDSR are collected when they are obtained for clinical care so that no extra visits or procedures are needed. These samples may include blood, bone marrow, skin cells, saliva, or discards from other clinical procedures. Family members may also contribute blood samples. All information obtained by the SDSR is housed on a secure, HIPAA-compliant database. No personal information is shared outside of the study team.

Peripheral blood, bone marrow, skin cells, saliva or a buccal swab, and discards from clinical procedures may be collected.

Shwachman Diamond Syndrome Registry and Study

Shwachman Diamond Syndrome Registry and Study (SDS Registry)

The SDSR will collect clinical information regarding SDS and SDS-Like conditions. The goal is to understand the natural history, treatment outcomes and complications of these rare disorders in order to improve diagnosis, medical management, and treatment.

The SDSR will coordinate a repository of blood, cord blood, bone marrow, saliva, skin fibroblast, and tumor samples and cell lines from patients with SDS and SDS-Like conditions for basic science studies of molecular and genetic pathways causing these disorders and their complications. We will also study how genetic/molecular pathways may be targeted or corrected for the development of new therapies. To this end, we will create immortalized cell lines including EBV-transformed lymphoblasts, immortalized fibroblasts, and induced pluripotent stem cells. These cell lines will provide a renewable source of rare patient-derived material for these studies.

The SDSR will sequence DNA from patient samples to try to identify new genes that are involved in SDS/SDS-like phenotypes.

The SDSR will disseminate information through the study website, conferences, and other scientific publications.

Children's Hospital Medical Center, Cincinnati

Boston Children's Hospital

Director, Bone Marrow Failure and Myelodysplastic Syndrome Program

Preleukemia

Myelodysplastic Syndromes

Anemia

Anemia, Aplastic

Cytopenia

Aplastic Anemia

Patients undergo red blood cell transfusions (RBCT) based on their perception and/or the presence of anemia symptoms for up to 6 months.

Red Blood Cell Transfusions (RBCT)

Ana Antun, MD

This pilot study evaluates safety of administration of red blood cell transfusions requested by patients based on their symptoms instead of levels of hemoglobin for the treatment of chronic anemia in patients with blood disorders.

PRIMARY OBJECTIVE:

I. To assess feasibility and safety of red blood cell transfusions at the time subjects requested based on symptomatic anemia.

SECONDARY OBJECTIVES:

I. To define a patient-driven red blood cell transfusion (RBCT) threshold and to compare the median hemoglobin (hgb) at the time subjects request RBCT to the standard threshold of hgb \< 8 g/dL.

II. To compare the number of red blood cell (RBC) units transfused and the frequency of transfusions at the time subjects request RBCT during the study period to the number of RBC units received and frequency using the standard threshold hemoglobin \< 8 g/dL during a comparable period prior to enrollment.

III. To compare the quality of life (QoL) scores when subjects request RBCT to the scores obtained at the time hgb is 8 +/- 0.5 g/dL.

OUTLINE:

Patients undergo RBCT based on their perception and/or the presence of anemia symptoms for up to 6 months.

After completion of study treatment, patients are followed up for 30 days.

Patient-Driven Transfusion Thresholds in Hematological Disorders: A Pilot Study

Frequency, duration, and severity of AEs and severe adverse events will be determined. The proportion of subjects with serious side effects will be calculated with 95% confidence interval. Descriptive statistics will be used to characterize subjects enrolled on the trial: age, sex, race and diagnosis.

The frequency of RBC units transfused will be compared between study period and prior to enrollment for the same patient (e.g. each patient will serve his/her own control) by Wilcoxon's sign rank test.

Hemoglobin concentration (Hgb) will be measured in g/dL.

The number of RBC units transfused will be compared between study period and prior to enrollment for the same patient (e.g. each patient will serve his/her own control) by Wilcoxon's sign rank test.

Will be compared to QoL scores at the time subjects request RBCT by paired t-test and/or Wilcoxon sign rank test.

Will be compared to QoL scores at the time hgb is 8 +/- 0.5 g/dL by paired t-test and/or Wilcoxon sign rank test.

Emory University

Principal Investigator

Immune System Diseases

Heart and Blood Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Hodgkin Disease

Myeloproliferative Disorders

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Antiviral Agents

Antilymphocyte Serum

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

CONDITIONING REGIMEN: Patients receive ATG IV over 4 hours on days -9 to -7, and fludarabine IV over 1 hour on days -6 to -3, then undergo TBI on day -1.

TRANSPLANT: Patients undergo PBSCT IV over 30-60 minutes on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days +3 and +4 and cytokine-treated veto cells IV over 30-60 minutes on day +7.

Anti-Thymocyte Globulin

Cytokine-treated Veto Cells

Peripheral Blood Stem Cell Transplantation

Total-Body Irradiation

Richard E. Champlin

Richard E Champlin

This phase I/II trial studies how well cytokine-treated veto cells work in treating patients with hematologic malignancies following stem cell transplant. Giving chemotherapy and total-body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Cytokine-treated veto cells may help the transplanted donor cells to develop and grow in recipients without causing graft-versus-host-disease (GVHD - when transplanted donor tissue attacks the tissues of the recipient's body).

PRIMARY OBJECTIVE:

I. To determine the optimal dose of anti-viral veto cells, defined as the dose which achieves engraftment without severe graft-vs-host disease (GVHD) at 42 days after non-myeloablative megadose T cell depleted haploidentical hematopoietic cell transplantation (HCT).

SECONDARY OBJECTIVES:

I. Toxicity. II. Response rate. III. Time to progression. IV. Infections. V. Immune reconstitution. VI. Overall survival up to 1 year.

OUTLINE: This is a dose-escalation study of cytokine-treated veto cells.

CONDITIONING REGIMEN: Patients receive anti-thymocyte globulin (ATG) intravenously (IV) over 4 hours on days -9 to -7 and fludarabine IV over 1 hour on days -6 to -3, then undergo total body irradiation (TBI) on day -1.

TRANSPLANT: Patients undergo peripheral blood stem cell transplantation (PBSCT) IV over 30-60 minutes on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days +3 and +4 and cytokine-treated veto cells IV over 30-60 minutes on day +7.

After completion of stem cell transplant, patients are followed up once a week for 4 weeks, once a month for 3 months, and then periodically for one year.

Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant

Anti-Viral Central Memory CD8 Veto Cells in Haploidentical Hematopoietic Stem Cell Transplantation

For the purpose of dose-finding, toxicity is defined as steroid resistant grade 3 or 4 graft-versus-host-disease (GVHD), or death from any cause, within 42 days of veto cell infusion.

Efficacy is defined as the patient being alive and engrafted at day 42 post veto cell infusion.

Unadjusted distributions of time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and veto cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Shwachman Diamond Syndrome Registry and Study	NCT06056908	Shwachman-Diamo... Shwachman-Diamo...		-	Boston Children's Hospital
Patient-Driven Transfusion Thresholds in Hematological Disorders: A Pilot Study	NCT03086252	Anemia Aplastic Anemia Bone Marrow Fai... Hematopoietic a... Leukemia Myelodysplastic...	Red Blood Cell ...	19 Years -	Emory University
Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant	NCT03622788	Acute Lymphobla... Acute Myeloid L... Aplastic Anemia Bone Marrow Fai... Chronic Lymphoc... Chronic Myeloge... Follicular Lymp... Hodgkin Lymphom... Mantle Cell Lym... Myelodysplastic... Myeloproliferat... Non-Hodgkin Lym... Plasma Cell Mye...	Anti-Thymocyte ... Cyclophosphamid... Cytokine-treate... Fludarabine Peripheral Bloo... Total-Body Irra...	12 Years - 75 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for bone marrow failure